Background: Acute coronary syndrome (ACS) is a potentially life-threatening condition which is more common in elderly people, and young are relatively protected. Currently, the protective effect on young from coronary artery disease (CAD) is taken away by several risk factors. The aim of this study is to determine the conventional risk factors and angiographic correlation of CAD in young age (<40 years) to that of elderly age (>40 years). Materials and Methods: This study was a hospital-based retrospective cross-sectional analytical study involving 1151 patients of ACS admitted in the cardiac ICU from May 2016 to May 2018. Among these patients, coronary risk factors such as smoking, diabetes, hypertension, dyslipidemia, and family history were studied. Patients were divided into two groups, Group A: <40 years and Group B: >40 years. Patients were evaluated angiographically. The significance of each risk factor between the groups was calculated by employing the Chi-square test and P < 0.05 was taken as statistically significant. Results: A total of 1151 cases were included in the study, of which 120 cases were <40 years of age. The prevalence of CAD in young in our study is 10.42% with male preponderance. P value is statistically significant (P < 0.05) among younger individuals for smoking, dyslipidemia, obesity, family history. Of 120 cases with critical CAD, single-vessel disease (SVD), predominantly the left anterior descending artery, was the most prevalent. SVD and recanalized coronaries were statistically significant among younger group whereas triple-vessel disease (TVD) is statistically significant among the elderly. Thrombus burden is more in young when compared to the elderly. Conclusion: Although ACS is a less common entity in young adults aged 40 years or less, recent epidemiological trend is progressing and it constitutes an important challenge both for a patient and for a treating physician. Young patients with CAD are mainly males, and SVD is more common. Emphasis should be given on diagnosis and management of risk factors in this vulnerable group to prevent mortality and morbidity.

Coronary artery disease (CAD) is an emerging health problem in India; various risk factors contribute to the increased prevalence of CAD in different age groups. Cardiovascular diseases (CVDs) and its complications account for approximately 12 million deaths annually in the Indian subcontinent.[1] The Global Status Report on noncommunicable diseases (NCDs) has reported that in India, CVD caused more than 2.5 million deaths in 2008. The leading cause of NCD deaths in 2012 was CVD (17.5 million deaths, or 46.2% of NCD deaths). As per 2014 statistics by the World Health Organization, 26% of total mortality in India is contributed by CVD.[2] Mortality due to CAD is higher in South India.[1] The mean age for the first presentation of acute myocardial infarction (MI) in Indians is 53 years.[3] Studies carried out in India, and other places suggest that Asians in general and Indians in particular are at an increased risk of MI at a younger age (<40 years).[4] Heart diseases are rising in Asian Indians and present 5–10 years earlier than in other populations around the world.

Various studies had considered the age limit varying from 35 to 55 years in the spectrum of young CAD.[2],[5] The onset of CAD before 40 years of age is considered as premature CAD (PCAD).[6],[7]

In our study, the incidence of CAD in young Indians is about 12%–16%, which is higher than any other ethnic group.[4],[8] Several studies were done analyzing the risk factors of CAD in young such as Multinational MONItoring of trends and determinants in CArdiovascular disease study,[9] INTERHEART,[4] and EURO HEART ACS epidemiologic studies,[10] along with randomized controlled trials, have shown that certain risk factors such as family history, obesity, dyslipidemia, and use of tobacco products, are more potent predictors of outcomes in the young than in their older counterparts. Very limited data are available regarding the prevalence of various risk factors for CAD in younger patients in our part of South India (Andhra Pradesh). Keeping this in view, a preliminary study was carried out to compare the conventional risk factors in young and elderly in patients with ACS. This study also includes the assessment of critical CAD (>70% diameter stenosis) in both groups angiographically. To our knowledge, this is one of pioneer studies focusing on the assessment of conventional risk factors for CAD with angiographic analysis at a tertiary teaching hospital in this part of the country.

Materials and Methods

Based on the inclusion criteria, a total of 1151 acute coronary syndrome (ACS, ST-elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], and unstable angina [USA]) patients admitted in the intensive critical care unit of the Department of Cardiology, ASRAM Medical College, between May 2016 and May 2018 after taking proper consent were included. Chronic stable angina patients and patients with ACS who did not undergo angiogram were excluded. The institutional ethical clearance was obtained. These study patients were divided into two groups; Group 1: <40 years of age and Group 2: >40 years of age. A detailed history (including personal and family history) and examination were noted. All patients were subjected to complete hematological and biochemical investigations including troponin-T and electrocardiogram for the evaluation of ACS. Among these patients, coronary risk factors such as smoking, diabetes mellitus, hypertension, dyslipidemia, gender, kidney disease, and angina class were studied. The body mass index (BMI) was also calculated for all the patients using Broca's formula. These patients were evaluated with echocardiogram for ejection fraction. Both the groups underwent coronary angiography (CAG) based on the American College of Cardiology/European Society of Cardiology indications for CAG.[11],[12] CAG was done through the right radial route using an optitorque catheter after taking patient's consent. Critical CAD was defined as 70% or more narrowing of a coronary artery that results in a significant reduction in maximum flow capacity in a distal vascular bed.[13] The patients were grouped into single-vessel disease (SVD), double-vessel disease, and triple-vessel disease (TVD) according to the number of major epicardial coronary arteries (left anterior descending artery [LAD], left circumflex artery, and right coronary artery [RCA]) involved.

The statistical significance of each risk factor between the groups was done using GraphPad Software (Dr. Harvey Motulsky GraphPad Software 2365 Northside Dr. Suite 560 San Diego, CA) in which we used a frequency percentage and Chi-square with Yates' correction at the level of significance α = 0.05 (P < 0.05).

Results

Of the 1151 cases included in this study, 120 were in the younger age group (<40 years) contributing 10.42% of the total cases. The mean age of CAD in young is 36.11 years, the youngest being 22 years. The mean age of presentation of older group is 56.42 years. Male outnumbered females in both groups. Of the 120 patients in the younger group, there were 86 (71.66%) males and 34 (28.33%) females. In the older group, males and females contributed 59% (608) and 41% (423), respectively. The mean BMI in younger group is 28.2 ± 5.3, whereas in the older group, it is 25.8 ± 6.1. Of 120 cases, anterior wall MI contributes the major portion of ACSs (43.3%) followed by inferior wall MI (26.66%), NSTEMI (10.83%), and USA (10.83%). The same order of incidence is followed among the elderly group with anterior wall contributing to 32%. The baseline characteristics are presented in [Table 1].

Various risk factors such as diabetes, hypertension, dyslipidemia, smoking, obesity, and chronic kidney disease (CKD) have been studied extensively in these two groups. Risk factors for CAD among the young and elderly patients are summarized in [Table 2] and presented in [Figure 1] with statistical analysis.

Table 2: Risk factors for acute coronary syndrome among young and elderly

Ejection fraction in both groups is tabulated in [Table 3]. In younger group, there is predominant moderate left ventricular (LV) dysfunction (35.83%) while severe LV dysfunction is extremely significant in older age group. The LV dysfunction profile is shown in [Figure 2] as a bar diagram.

Table 3: Comparison of various classes of left ventricle dysfunction in two age groups

Angiographic data are depicted in [Table 4]. SVD and recanalized coronaries were statistically significant among younger group (P < 0.05), whereas TVD is statistically significant among older group (P < 0.05). Thrombus burden is more in young when compared to the elderly. The predominant vessel involved in the younger and older groups is LAD contributing to 68.3% and 63.62%, respectively. [Figure 3] shows the pie diagram depiction of angiographic profile of the two groups.

Table 4: Comparison of angiographic characteristics of acute coronary syndrome in age <40 years and >40 years

The global burden of CVDs is on rapid rise due to a predominant increase in the incidence and prevalence of the same in the developing countries. India, a developing nation, is following the same trend. During the past three decades, the prevalence of most of the cardiovascular risk factors including smoking, diabetes mellitus, hypertension, and dyslipidemia has increased markedly in India.[14],[15]

About 25% of acute MI in India occurs under the age of 40 and 50% under the age of 50.[15] One center in Kerala reported a 47-fold increase in the incidence of first MI under the age of 40 in the last 20 years.[8] In general, MI develops 5–10 years earlier in Asian Indians than in other populations [16],[17] and its occurrence in patients under 40 is 5- to 10-fold higher.

In Global Registry of Acute Coronary Events study, the prevalence of young ACS was 6.3%;[16] in Thai ACS registry, it was 5.8%;[17] in Spain registry, it was 7%.[18] In our study, the prevalence of young ACS is 10.42%. In our study, a total of 120 patients were <40 years of age. Most of them had anterior MI, and these patients were treated more aggressively as compared to older patients. This is consistent with previous reports.[19],[20],[21] Previous studies have shown that male gender is one of the classic risk factors for CAD.[22],[23] In our study, the incidence of ACS in young males is 71.66%. Our study also concurs with previous findings that overall risk factors were more likely in males when compared to females.

Family history of PCAD is an important risk factor for young CAD. It stresses the role of genes in the etiology of young CAD. Studies have shown that person with positive family history of PCAD tends to have severe coronary atherosclerosis and is a very strong predictor of future acute coronary event.[24] Increased plaque content in coronary vessels is seen in individuals with positive family history of PCAD and increases the incidence of severe obstructive CAD. In a study done in London, Chen et al.[25] had found family that history of CAD was 39% in young ACS patients. Cole et al. revealed that around 64% of young patients had a positive family history.[26] Family history of CAD was found in 30% of our younger group.

Tobacco smoking is an important independent risk factor for CAD in young adults. Current smoking of >10 cigarettes or beedi a day is associated with a 6.7-fold increase in the risk of MI.[27] The risk of CAD begins to decline within months of smoking cessation and disappears within 3–5 years. A few studies have estimated smoking prevalence at 28.5%–30% in Indians living in India.[28] The effect of cigarette smoking on coronary risk factors is pervasive. Unfavorable effects include enhancement of platelet function. Platelet activation by cigarette smoking is linked to thrombosis formation, including onset of MI.[29] Zimmerman et al. found a prevalence of smoking in 92% of young CAD patients.[30] Mukherjee et al. found prevalence of smoking to be higher in those <40 years of age, compared to those of >40 years (58.7% vs. 43%).[31] The proportion of smoking among young people has declined, but the overall proportion maintains a high ratio.[5] Pais et al. have shown it to be the most dominant risk factor in Indian population studied.[27] Our study showed that smoking is a major risk factor for CAD in both study groups. The prevalence of smoking was 25.8% in younger group of our study. Smoking is statistically significant among young adults when compared to the elderly. Our study also demonstrates that cigarette smoking was the dominant risk factor predisposing to an earlier onset of CAD, in line with previous studies.[32],[33]

Indians are genetically prone to develop type-2 diabetes mellitus due to insulin resistance. Hyperinsulinemia in these patients accelerates the atherosclerotic process in the coronary arteries. Diabetes is second only to CAD as a health burden in India. During the past decade, the number of people with diabetes in India increased from 32 million to 50 million, and this figure may reach 87 million by 2030.[34] Hyperinsulinemia, insulin resistance, and higher rate of prevalence of metabolic syndrome in people with type-2 diabetes were attributed to high coronary risk in South Asians.[35],[36] In our study, slightly higher incidence of diabetes was seen among the elderly group (20.9%) when compared to younger group (20%), but no statistical significance was noted when comparison was made among the two groups. This fact has been documented in a number of previous studies.[33]

The exact mechanism through which systemic hypertension induces MI has not been studied in detail, but there is evidence that hypertension causes LV hypertrophy and progression of atherosclerosis, resulting in CAD.[37] Hypertension was revealed as a significant risk factor among the young in the studied population. This agrees with the previous studies by Sofia and EUROSPIRE, where hypertension has been seen as a major risk factor for CAD,[38] but no statistical significance is attributed.

Dyslipidemia is defined as total cholesterol (TC) >200 mg/dl, low-density lipoprotein (LDL) >100 mg/dl, triglycerides (TG) >150 mg/dl, high-density lipoprotein (HDL) <40 mg/dl, according to the NCEP-ATP3 guidelines.[39] An elevated level of TC is the strongest risk factor for CAD. A recent large study has shown an 8-fold higher CAD mortality with an increase in TC from <160 to >280 mg/dL among young Americans.[40] An 88 mg/dL increase in TG levels significantly increases the relative risk (RR) of CAD by 30% in men and 75% in women.[41] Low HDL is associated with increased risk of CAD even if TG and TC levels are not elevated. A 10 mg/dL decrease in HDL confers the same risk for CAD as 30 mg/dL increase in LDL. Low HDL with or without high TG is very common among Indians and genetic factors may be involved. Conversely, people with low TG-high HDL levels have a low risk of CAD, but this profile is uncommon among Asian Indians.[42]

It is documented that South Asians have TC and LDL-cholesterol levels comparable to Afro-Caribbean's and Whites, but they do have higher TG and low HDL-cholesterol levels.[27] Although dyslipidemia is an important risk factor for young CAD, there seems to be a little difference in the prevalence of lipid abnormalities in younger and elderly. One study demonstrated a significantly increased level of LDL and TC in persons of CAD >55 years of age when compared to <55 years of age.[43] Conversely, in another study, there is high prevalence of lipid abnormalities in young CAD when compared to older group.[44] These differences in lipid parameters may be due to effect of dietary, genetic, and environmental factors on lipid metabolism. Studies on epidemiological data from angiographically proven cases of PCAD (≤40 years) in native Indians suggest hyperlipidemia as the most prevalent risk factor.[45],[46] In our study, the fasting lipid profile tests revealed evidence of dyslipidemia in 17.5% of the young patients and 9% of the elderly subjects. This is statistically significant among younger group. The proposed reason of elderly patients having less incidence of abnormal lipids in our study is that most of the patients were already using some form of lipid-lowering drugs prescribed earlier.

Obesity is associated with increased risk of hypertension, diabetes, dyslipidemia, and CAD. Marked adverse metabolic consequences are seen with central (android or apple-type), but rarely with gluteo-femoral (gynoid or pear-type) obesity. Sagittal abdominal diameter to skin fold ratio seems to be a good indicator in predicting PCAD, even better than BMI and waist circumference.[47] Obesity is a well-established risk factor for CAD, particularly in urban India. From previous studies, there is little difference in the prevalence of obesity in young CAD when compared to older CAD patients. In view of obesity as the risk factor for CAD, based on the BMI, our study showed statistically significant prevalence of higher BMI in Group 1 (<40 years) compared to Group 2 (>40 years). Although most of the comorbidities relating obesity to CAD increase as BMI increases, they also relate to body fat distribution. Asians have a higher body fat percentage for a given BMI than other ethnic groups and a different fat distribution pattern and are more prone to central obesity at low BMI levels.[48] It might indicate that obesity as such not only relates to but also independently predicts coronary atherosclerosis. High-intensity aerobic exercise [49] and moderate alcohol intake have been known to reduce risk of CAD and MI.

Our study also showed that elderly patients with CKD had an 11% prevalence of CAD. In 1998, the U.S. National Kidney Foundation Task Force on Cardiovascular Disease in Chronic Renal Disease recommended that patients with CKD be considered to belong to the highest risk group for the development of cardiovascular events.[50] These patients present unique challenges to physicians attempting to manage concomitant ischemic heart and CKD.

We observed an age-dependent variation in hazard associated with smoking and hypertension, with greater relative hazard in the youngest cohort of patients. However, diabetes mellitus and kidney disease were more prevalent in elderly patients in this study. Finally, in our study, significant risk factors in younger age group were found to be family history, smoking, dyslipidemia, and obesity. The CLARIFY registry shows a high prevalence and poor control of cardiovascular risk factors in patients from India. Efforts to improve risk factor control are required.[51] All the studies comparing risk factor profiles are tabulated in [Table 5].

In our study, younger group showed predominantly moderate LV dysfunction (35.83%), whereas in the elderly, severe LV dysfunction is predominant (49.8%). This is consistent with results from other studies.[52],[53] Cole et al. had identified average ejection fraction of 55% in young adults.

ACS in young, based on angiographic characteristics, can be due to atherosclerotic and nonatherosclerotic CAD which includes arteritis, thrombosis, embolization, and spasm (cocaine abuse). Coronary artery thrombus can be seen in hypercoagulable states such as protein C and S deficiency, antiphospholipid antigen (APLA), and nephrotic syndrome.[54],[55],[56]

In our study, all 120 young patients underwent coronary angiogram. Coronary angiographic data showed statistically significant predominance of SVD in 67.5% young adults which is in accordance with Pathak et al.,[57] Suresh et al.,[58] and al-Koubaisy et al.[59] Recanalized coronaries were seen in 15.8% of young patients which is concordant with other studies such as Maroszyńska-Dmoch et al.,[60] Sricharan et al.,[61] and Noor et al.[62] Thrombus burden is more in young when compared to elderly. The predominant vessel involved in younger age group is LAD contributing to 68.3%, which is in concordance with angiographic studies such as Badran et al.[63] and Ahmed Hussein.[64] However, Kennelly et al.[65] have found that RCA was the most common artery involved in their study done in 1982. There is only 3.3% of TVD in our study which is in accordance with Jamil et al.[66] and Sricharan et al.[61]

All the studies showing angiographic data in young adult are depicted in [Table 6] with appropriate references.

Although ACS, fortunately, is an uncommon entity in young adults aged 40 years or less, it constitutes an important challenge for both a patient and a treating physician. Prevention and control of premature cardiovascular diseases in India need urgent control of these factors. Smoking turned out to be the major risk factor which needs strict prevention. Target oriented control of hypertension, obesity, lipid levels, and glycemia are required. Young patients with ACS are mainly males, and SVD is more common with large thrombus burden. Younger group has predominance of moderate LV dysfunction, whereas, in the older group, there is predominance of severe LV dysfunction. Emphasis should be given to educating the young on the management of these risk factors to decrease mortality and morbidity related to ACS.

Kaul U, Natrajan S, Dalal J, Saran RK. Prevalence and control of cardiovascular risk factors in stable coronary artery outpatients in India compared with the rest of the world: An analysis from international CLARIFY registry. Indian Heart J 2017;69:447-52.